Activation of protein C during reperfusion in clinical liver transplantation

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Abstract
Activated protein C (APC) exhibits anticoagulant and antiinflammatory properties. We studied the kinetics and magnitude of protein C activation in clinical liver transplantation and the interaction of this activation with neutrophil and monocyte activation. In 10 patients undergoing liver transplantation, we measured plasma protein C and APC levels, neutrophil and monocyte CD11b and L-selectin expression, and leukocyte differential counts pre-, intra-, and postoperatively. Samples of blood entering and leaving the liver were obtained simultaneously to assess changes across the liver. Protein C level was low preoperatively (65%, range 39%-141%) and remained low throughout surgery. Compared with the preoperative level (107%, range 78%-161%), APC level increased during liver reperfusion (471%, range 183%-917%, P=0.05). A transhepatic decrease in protein C level (-16%, range -45%-5%, P=0.007), but not in APC level, occurred during initial liver reperfusion. At the same time, neutrophil and monocyte activation took place in the liver. Despite protein C deficiency, patients with liver insufficiency are able to maintain normal APC levels. During reperfusion, protein C consumption occurs in the liver without concomitant hepatic release of APC, indicating a shortage of APC in the reperfused liver. The process consuming protein C and APC may be related to the simultaneous ongoing neutrophil and monocyte activation within the liver graft, indicating a regulatory role for APC in inflammation.